crossing96/oncoscreening huggingface dataset:
Syphilitic and lymphogranuloma venereum (LGV) proctocolitis: clues to a frequently missed diagnosis.	A rising incidence of syphilis and lymphogranuloma venereum (LGV) underscores the importance of recognizing these sexually transmitted infections (STI) in routine anocolonic biopsies. To increase awareness of their morphologic manifestations, we undertook a clinicopathologic study of our experience: syphilis (7 patients, 7 specimens), LGV (2 patients, 4 specimens), and syphilis/LGV (1 patient, 3 specimens). The diagnoses of all study specimens were confirmed with pertinent clinical studies. All study patients were human immunodeficiency virus positive, and all 9 with available history were men who have sex with men. The majority presented with bleeding (9), pain (6), and tenesmus (4). Ulcerations were the most common endoscopic abnormality (7), whereas mass lesions were confined to the syphilis group (4). None of the initial impressions included LGV, and syphilis was prospectively suggested only by pathologists (6 of 8) without the knowledge of clinical information and on the basis of morphology. Alternative impressions included condyloma acuminatum (3), inflammatory bowel disease (3), and malignancy (2), among others. All study specimens shared the following histologic core features: an intense lymphohistiocytic infiltrate with prominent plasma cells and lymphoid aggregates, only mild to moderate acute inflammation, minimal basal plasmacytosis and crypt distortion, and only rare granulomas and Paneth cell metaplasia. The spirochetes were focally demonstrated on a Treponema pallidum immunohistochemical stain (1) but not on silver stains (3). All patients with available follow-up data showed resolution of symptoms and imaging abnormalities after STI therapy (6). In summary, we report a unique pattern of STI proctocolitis consistently identified in patients with serologically confirmed syphilis and/or LGV infection; pertinent STI therapy leads to resolution of clinical abnormalities. This histologic pattern is important to recognize for timely treatment, for prevention of onward STI transmission, and to avoid the diagnostic pitfalls of inflammatory bowel disease or malignancy.	bladder
N6-isopentenyladenosine and its analogue N6-benzyladenosine induce cell cycle arrest and apoptosis in bladder carcinoma T24 cells.	Cytokinins are phytohormones critically involved in the regulation of plant growth and development. They also affect the proliferation and differentiation of animal cells, thus representing new tools to treat diseases that involve dysfunctional cell growth and/or differentiation. Recently, by performing structure-function studies on human cells, we found that only N6-isopentenyladenosine and its benzyl analogue N6-benzyladenosine suppress the clonogenic activity and the growth of different neoplastic cells. We here broaden our studies on bladder carcinoma T24 cells, because, due to the high recurrence rate of bladder cancer, new active molecules are sought to contrast the growth of this tumor. Early events induced by N6-isopentenyladenosine and N6-benzyladenosine are the alteration of T24 cell morphology and the disorganization of the actin cytoskeleton. After 24 h N6-isopentenyladenosine and N6-benzyladenosine inhibit growth by arresting the cells in the G0/G1 phase of the cell cycle. We also show that the two compounds induce apoptosis, an event linked to the activation of caspase 3. Since DNA damage is a prime factor resulting in cell cycle arrest and apoptosis, it is noteworthy that we do not detect any genotoxic effect upon treatment of T24 cells with N6-isopentenyladenosine and N6- benzyladenosine. Because the disruption of actin filaments leads to G1 arrest and is also implicated in apoptosis, we hypothesize that cytoskeletal rearrangement might be responsible for triggering the antiproliferative and proapotpotic effects of N6-isopentenyladenosine and N6- benzyladenosine in T24 cells.	bladder
A multi-analyte assay for the non-invasive detection of bladder cancer.	Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. We performed a case-controlled validation study in which voided urines from 127 patients (64 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection. Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.	bladder
Urinary diversion--approaches and consequences.	BACKGROUND: Bladder cancer is not a rare disease: In 2010, there were more than 70 000 affected patients in the United States. Radical cystectomy for the treatment of muscle invasive bladder cancer necessitates urinary diversion. METHODS: We present the current options for urinary diversion and their different indications on the basis of a selective search for pertinent literature in PubMed and our own clinical experience. RESULTS: When bladder cancer is treated with curative intent, continence-preserving orthotopic urinary bladder replacement is preferred. For heterotopic urinary bladder replacement, a reservoir is fashioned from an ileal or ileocecal segment. Urine is diverted to the rectum by way of the sigmoid colon. When bladder cancer is treated with palliative intent, non-continence-preserving cutaneous urinary diversion is usually performed: The creation either of a renal-cutaneous fistula or a self-retaining ureteral stent is a purely palliative procedure. In these interventions, the resorptive surface of the bowel segment used can no longer play its original physiological role in the gastrointestinal tract, even though its absorptive and secretory functions are still intact. This has metabolic consequences, because the diverted urine here comes into contact with a large area of bowel epithelium. Early preventive treatment must be provided against potentially serious complications such as metabolic acidosis and loss of bone density. The resection of ileal segments can also lead to malabsorption. The risk of secondary malignancy is elevated after either continence-preserving anal urinary diversion (>2%) or bladder augmentation (>1%). CONCLUSION: There are four options for urinary diversion after cystectomy that can be performed when surgery is performed with either curative or palliative intent. There are also a number of purely palliative interventions.	bladder
Expression of survivin and livin predicts early recurrence in non-muscle invasive bladder cancer.	BACKGROUND: Survivin and livin are novel members of the inhibitor of apoptosis gene family (IAP) that controls mitotic progression and induces tumor cell invasion. This study aims to evaluate the association of both expression with clinical outcomes and risk of recurrence in patients with non-muscle invasive bladder cancer (NIMBC). PATIENTS AND METHODS: We investigated the expression of survivin and livin in 72 NMIBC samples using immunohistochemical staining (Envision Method). Survivin and livin were considered high-expressed when more than 10% of the cells expressed. The archival bladder tissue specimens from 11 normal controls were examined and studied. All patients with a follow-up of at most 5 years following initial transurethral resection (TUR) were included in the study. The association of both expression with established clinicopathologic factors and recurrence free survival (RFS) was analyzed using log-rank test and Cox regression analysis. RESUTS: Neither survivin nor livin was expressed in normal bladder urothelium. Survivin and livin were high-expressed in 84.7 and 75.0% of NIMBC. And in cases of recurrence, the high-expression (H-exp.) rates were 98.3 and 91.7% (P < 0.01), respectively. The recurrence of NIMBC was significantly associated with high expression of survivin and livin (P < 0.01, P < 0.01), and G-3 tumors had a significantly greater proportion of high survivin expression than G-1 or/and G-2 tumors (P = 0.01); however, no association was found between expression of both and age, gender, pathology stage, or adjuvant therapy. High expression of survivin (RR:9.818, 95% CI: 1.109-86.911, P = 0.040) and livin (RR: 4.199; 95% CI: 1.018-17.321; P = 0.047) was significantly powerful prognostic factors in Cox regression analysis for RFS. CONCLUSIONS: Expression of survivin and livin may influence the prognosis of NIMBC. This finding opens new perspectives for Survivin and livin prediction of early recurrence in NIMBC.	bladder
Female sex is an independent risk factor for reduced overall survival in bladder cancer patients treated by transurethral resection and radio- or radiochemotherapy.	PURPOSE: To evaluate sex as a possible prognostic factor in bladder cancer patients treated with transurethral resection (TURBT) and radio- (RT) or radiochemotherapy (RCT). METHODS: Kaplan-Meier analyses and multiple Cox proportional hazards regression analyses were performed to analyze sex as a possible prognostic factor on the overall (OS) and cancer-specific (CSS) survival of 386 male and 105 female patients who underwent TURBT and RCT or RT with curative intent between 1982 and 2007. RESULTS: After a follow-up of 5 years, female sex demonstrated a hazard ratio (HR) of 1.79 (95 % CI 1.24-2.57) for OS; for CSS, the HR was 2.4 (95 % CI 1.52-3.80). Sex was an adverse prognosticator of both OS and CSS independent from age at diagnosis, cT stage, grading, concurrent cis, LVI, focality, therapy response, resection status and therapy mode. Kaplan-Meier analysis showed significantly reduced OS of women compared with men, with a median survival of 2.3 years for female patients and 5.1 years for male patients (p = 0.045, log-rank test). The estimated median CSS was 7.1 years for female patients and 12.7 years for male patients (p = 0.11, log-rank test). CONCLUSIONS: Female sex is an independent prognostic factor for reduced OS and CSS in bladder cancer patients treated by TURBT and RT or RCT. These data are in agreement with those reported for OS after radical cystectomy in muscle-invasive bladder cancers. Therefore, further studies are strongly warranted to obtain more information about molecular differences regarding sex-specific carcinogenesis in bladder cancer and about possible therapeutic considerations.	bladder
A contemporary update on pathology standards for bladder cancer: transurethral resection and radical cystectomy specimens.	CONTEXT: Pathology standards for the diagnosis of bladder cancer (BCa) have recently evolved to better reflect patient diagnosis and clinical outcomes. OBJECTIVE: To update pathology reporting standards for BCa. EVIDENCE ACQUISITION: We searched the international medical literature and reviewed all articles that addressed BCa gross dissection, pathologic diagnosis, staging, and reporting as of June 6, 2012. We also reviewed the proceedings from the recent Second International Consultation on Bladder Cancer (Vienna, Austria). The literature selected for review focuses on evidence-based studies that address histopathologic factors in BCa, with emphasis placed on factors that influence patient diagnosis and clinical outcomes. EVIDENCE SYNTHESIS: We separated data into three main components for analysis based on the type of specimen obtained: (1) transurethral resection specimens, with an emphasis on pathologic staging, variants of urothelial carcinoma, angiolymphatic invasion, and relevant ancillary techniques such as immunohistochemistry in assessing these features; (2) cystectomy specimens, with an emphasis on pT0 disease, prostatic involvement by urothelial carcinoma and lymph node dissection and analysis; and (3) cytology correlates, with recommendations for the use of cytology paired with tissue-based sampling. Areas of controversy are described and recommendations based on existing guidelines are provided. The value of a multidisciplinary team is highlighted. CONCLUSIONS: Ongoing international collaborations amongst pathologists have led to emerging standards in the reporting and microscopic diagnosis of BCa specimens. Although some areas remain controversial, we present the most up-to-date data and guidelines relevant to neoplastic pathology of the urinary bladder.	bladder
miR-30d, miR-181a and miR-199a-5p cooperatively suppress the endoplasmic reticulum chaperone and signaling regulator GRP78 in cancer.	GRP78, a major endoplasmic reticulum chaperone and signaling regulator, is commonly overexpressed in cancer. Moreover, induction of GRP78 by a variety of anti-cancer drugs, including histone deacetylase inhibitors, confers chemoresistance to cancer, thereby contributing to tumorigenesis. Thus, therapies aimed at decreasing GRP78 levels, which results in the inhibition of tumor cell proliferation and resensitization of tumor cells to chemotherapeutic drugs may hold promise for cancer treatment. Despite advances in our understanding of GRP78 actions, little is known about endogenous inhibitors controlling its expression. As endogenous regulators, microRNAs (miRNAs) play important roles in modulating gene expression; therefore, we sought to identify miRNA(s) that target GRP78, under the hypothesis that these miRNAs may serve as therapeutic agents. Here, we report that three miRNAs (miR-30d, miR-181a, miR-199a-5p) predicted to target GRP78 are down-regulated in prostate, colon and bladder tumors, and human cancer cell lines. We show that in C42B prostate cancer cells, these miRNAs down-regulate GRP78 and induce apoptosis by directly targeting its 3' untranslated region. Importantly, we demonstrate that the three miRNAs act cooperatively to decrease GRP78 levels, suggesting that multiple miRNAs may be required to efficiently control the expression of some genes. In addition, delivery of multiple miRNAs by either transient transfection or lentivirus transduction increased the sensitivity of cancer cells to the histone deacetylase inhibitor, trichostatin A, in C42B, HCT116 and HL-60 cells. Together, our results indicate that the delivery of co-transcribed miRNAs can efficiently suppress GRP78 levels and GRP78-mediated chemoresistance, and suggest that this strategy holds therapeutic potential.	bladder
The sensitivity of initial transurethral resection or biopsy of bladder tumor(s) for detecting bladder cancer variants on radical cystectomy.	PURPOSE: We determined the ability of bladder biopsy and transurethral resection of the bladder to accurately predict bladder cancer variants on radical cystectomy since certain variants may affect prognosis and treatment. MATERIALS AND METHODS: We retrospectively evaluated the records of 302 patients who underwent biopsy and/or transurethral resection of the bladder followed by radical cystectomy from 2008 to 2010. The frequency of variant morphology and the sensitivity of the precystectomy material was determined using pathological findings at radical cystectomy as the final result. RESULTS: Bladder cancer variants were identified in 159 patients (53%) on initial biopsy/transurethral resection and/or final pathological evaluation at radical cystectomy. The most common variant was urothelial carcinoma with squamous differentiation in 72 of 159 patients (45%), followed by micropapillary urothelial carcinoma in 41 (26%). In 9 patients (6%) variant morphology was identified only on biopsy/transurethral resection bladder and not on final radical cystectomy pathological assessment. The remaining 150 patients (94%) showed variant morphology on radical cystectomy with (79 or 53%) or without (71 or 47%) variant morphology on the preceding biopsy/transurethral resection. The sensitivity of variant detection showed a broad range by variant subtype. Overall, initial biopsy/transurethral resection sensitivity was 39% for predicting variant morphology on radical cystectomy. CONCLUSIONS: Overall sensitivity for predicting bladder cancer variants from biopsy/transurethral resection of the bladder sampling is relatively low. This is likely due to sampling and tumor heterogeneity rather than to an inaccurate pathological diagnosis. Additional predictive markers of variant morphology may be useful to determine which tumors contain aggressive variants that may alter outcomes or therapy.	bladder
Understanding the use of immediate intravesical chemotherapy for patients with bladder cancer.	PURPOSE: Despite its established efficacy in reducing recurrence rates for patients with urothelial carcinoma, immediate intravesical chemotherapy is reportedly used infrequently. Accordingly, the Urological Surgery Quality Collaborative implemented a project aimed at understanding and improving the use of immediate intravesical chemotherapy. MATERIALS AND METHODS: Surgeons in 5 Urological Surgery Quality Collaborative practices prospectively collected clinical and baseline intravesical chemotherapy use data for patients undergoing bladder biopsy or transurethral bladder tumor resection from September 2010 through January 2012. In the second phase of data collection (June 2011 through January 2012) treating surgeons also documented reasons for not administering intravesical chemotherapy. We defined patients with 1 to 2 clinical stage Ta/T1, completely resected, papillary tumor(s) as ideal candidates for treatment with immediate intravesical chemotherapy. For ideal and nonideal patients we examined baseline use of intravesical chemotherapy across Urological Surgery Quality Collaborative practices as well as reasons for not administering therapy among ideal patients. RESULTS: Among 1,931 patients 37.2% met criteria as ideal cases for intravesical chemotherapy administration. We observed significant variation in the use of intravesical chemotherapy across Urological Surgery Quality Collaborative practices for ideal (range 27% to 50%) and nonideal cases (9% to 24%) (p <0.001). Reasons for not treating ideal candidates included lack of confirmation of malignancy (4, 2.8%), uncertainty regarding the benefits of intravesical chemotherapy (28, 19.6%) and logistic factors such as the unavailability of medication (34, 23.8%). CONCLUSIONS: Use of immediate intravesical chemotherapy by Urological Surgery Quality Collaborative practices is higher than reported elsewhere but still varies widely, even among ideal candidates. Efforts to optimize use will be aided by disseminating evidence supporting indications and benefits of intravesical chemotherapy, and by addressing local logistic factors that limit access to this evidence-based therapy.	bladder
Shorter recurrence-free survival time, higher risk of multiple recurrences: a retrospective study of non-muscle invasive bladder cancer after transurethral resection.	BACKGROUND: Multiple recurrences are common in non-muscle invasive bladder cancer, but the risk of multiple recurrences has not been fully described. Identifying patients at high risk of multiple recurrences will help to select an optimal therapeutic strategy and to improve prognosis. This study was conducted to identify the risk factors for multiple recurrences of non-muscle invasive bladder cancer. METHODS: We reviewed the clinical data of all patients with non-muscle invasive bladder cancer in our hospital between January 2003 and February 2010. Patients with at least one recurrence were included. Multivariate analysis was performed for theorized risk factors (age, gender, tumor stage, grade, size, location, number of lesions, adjuvant intra-vesical chemotherapy after transurethral resection, and recurrence-free survival after each resection) to clarify risk factors for multiple recurrences of non-muscle invasive bladder cancer. RESULTS: Of the 278 patients with non-muscle invasive bladder cancer, 84 were with at least one recurrence and a total of 222 recurrences among them were followed up for 6 - 70 months (mean, 36.1 months). Recurrence-free survival after initial resection predicted the overall frequency of bladder cancer recurrence (risk ratio (RR) = 37.83, 95% confidence interval (CI) = 3.45 - 396.13, P = 0.001) and second recurrence (RR = 6.15, 95%CI = 1.28 - 29.57, P = 0.023). Similarly, recurrence-free survival after a second resection was the only significant risk factor for third recurrence (RR = 31.08, 95%CI = 2.53 - 381.47, P = 0.007). Moreover, recurrence-free survival after initial resection was the only significant factor to predict later progression to muscle invasive bladder cancer (RR = 8.62, 95%CI = 1.47 - 58.34, P = 0.001). CONCLUSIONS: Recurrence-free survival after resection is an independent predictor of multiple recurrences of non-muscle invasive bladder cancer. The shorter the period between resection and recurrence is, the higher the risk of multiple recurrences.	bladder
Molecularly modified VP3 (30-121) induces apoptosis in human bladder cancer (EJ) cells but not in normal (3T3) cells.	The chicken anaemia virus protein 3 (VP3 or apoptin) induces apoptosis specifically in tumour and transformed cells but not in normal cells. This selective apoptosis is ideal for therapeutic purposes. However, VP3, a heterologous protein, is immunogenic in vivo. Such a drawback limits its clinical usage. To diminish its potential immunogenicity, we modified the sequence of VP3. The VP3 genes functional sequence starts at 33 AA (amino acids) from the N-terminal side, and the first protein structural domain consists of 30 AA. We found that the first domain of VP3 contains no functional sequences. Therefore, this domain was removed to test whether its absence affects apoptosis. Transfection of EGFP (enhance green fluorescent protein)-modified-VP3 or HA-modified-VP3 in bladder cancer cell lines (EJ) resulted in its expression, successful localization to the nucleus and efficient induction of apoptosis. Expression of EGFP-modified-VP3 or HA-modified-VP3 had no influence on mouse fibroblast cells (3T3). The modified VP3 (30-121), like the wild-type VP3, induced EJ cell apoptosis without affecting 3T3 cells. This study increases our understanding of modified VP3 (30-121) as a possible substitute for the wild-type VP3, which makes VP3 (30-121) an interesting candidate for the development of novel therapeutic strategies.	bladder